Safety Assessment of Inorganic Hydroxides as Used in Cosmetics

Safety Assessment of Inorganic Hydroxides

as Used in Cosmetics

Status: Scientific Literature Review for Public Comment

Release Date: June 18, 2015

Panel Meeting Date: September 21-22, 2015

All interested persons are provided 60 days from the above release date to comment on this safety assessment and to

identify additional published data that should be included or provide unpublished data which can be made public

and included. Information may be submitted without identifying the source or the trade name of the cosmetic

product containing the ingredient. All unpublished data submitted to CIR will be discussed in open meetings, will

be available at the CIR office for review by any interested party and may be cited in a peer-reviewed scientific

journal. Please submit data, comments, or requests to the CIR Director, Dr. Lillian Gill.

The 2015 Cosmetic Ingredient Review Expert Panel members are: Chairman, Wilma F. Bergfeld, M.D., F.A.C.P.;

Donald V. Belsito, M.D.; Ronald A. Hill, Ph.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; James G.

Marks, Jr., M.D.; Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR

Director is Lillian J. Gill, DPA. This safety assessment was prepared by Christina L. Burnett, Scientific

Analyst/Writer and Bart Heldreth, Ph.D., Chemist CIR.

1620 L St NW, Suite 1200 ◊ Washington, DC 20036-4702 ◊ ph 202.331.0651 ◊ fax 202.331.0088

◊ cirinfo@cir-safety.org

INTRODUCTION

This report addresses the safety of the inorganic hydroxides calcium hydroxide (also known as calcium hydrate or

slaked lime), magnesium hydroxide, potassium hydroxide (potassium hydrate or potash), and sodium hydroxide (sodium

hydrate, lye, or caustic soda). These ingredients are all alkaline salts and are reported to function as pH adjusters in

cosmetics.

The inorganic hydroxides in this report, with the exception of magnesium hydroxide, are well known caustic agents

that can cause severe burns and corrosion with acute exposures. Sodium hydroxide is commonly used as a positive control in

efficacy studies of skin protective creams and in other studies of irritant contact dermatitis.

Some chemical and toxicological data on the inorganic hydroxides included in this safety assessment were obtained

from robust summaries of data submitted to the European Chemical Agency (ECHA) by companies as part of the REACH

chemical registration process. These data summaries are available on the ECHA website.

3-6

CHEMISTRY

Definition

Inorganic hydroxides are alkaline salts formed by treating oxides with water or via decomposing salts by adding

other soluble hydroxides to a solution thereof (e.g., adding sodium hydroxide to magnesium sulfate will produce magnesium

hydroxide). The formation of an inorganic hydroxide, such as specifically lime or calcium hydroxide, by reaction of an oxide

with water is a known as slaking.

The resulting highly water soluble ingredients only vary structurally by the metal cation.

These variations result in different degrees of alkalinity across these four ingredients, ranging in pK

values from 0.2 to 4.0.

Used primarily as pH adjusters (to increase the pH of an otherwise acidic formulation), the caustic nature of these ingredients

is unlikely to be observable in typical, final cosmetic formulations.

Figure 1. Inorganic Hydroxides (wherein “M” is group I or II metal)

The definitions, structures, and functions of the inorganic hydroxides included in this report are provided in Table 1.

Chemical and Physical Properties

The inorganic hydroxides are all highly water soluble, white solids with specific gravities around 2. Physical and

chemical properties of the inorganic hydroxides in this report are provided in Table 2.

Method of Manufacturing

Calcium Hydroxide

Calcium hydroxide may be formed by the hydration of lime or treating an aqueous solution of a calcium salt with

alkali.

Magnesium Hydroxide

Magnesium hydroxide may be formed by reacting magnesium chloride or sulfate and sodium hydroxide.

Most

commercial-grade magnesium hydroxide is obtained from seawater or brine using lime or dolomitic lime.

Potassium Hydroxide

Potassium hydroxide may be produced by treating oxides with water, known as brine electrolysis.

7,8

Sodium Hydroxide

Sodium hydroxide is formed by brine electrolysis.

2 NaCl + 2 H

O → 2 NaOH + Cl

+ H

Formula 1. Brine Electrolysis

Sodium hydroxide may also be formed by reacting lime with soda ash.

Ca(OH)

+ Na

→ CaCO

+ 2 NaOH

Formula 2. Slacking

USE

Cosmetic

The safety of the cosmetic ingredients included in this safety assessment is evaluated on the basis of the expected

use in cosmetics. The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) utilizes data received from the Food and Drug

Administration (FDA) and the cosmetics industry in determining the expected cosmetic use. The data received from the

FDA are those it collects from manufacturers on the use of individual ingredients in cosmetics by cosmetic product category

in its Voluntary Cosmetic Registration Program (VCRP), and those from the cosmetic industry are submitted in response to a

survey of the maximum reported use concentrations by category conducted by the Personal Care Products Council (Council).

According to the 2015 VCRP survey data, sodium hydroxide has the most reported uses of the ingredients listed in

this safety assessment in cosmetic products, with a total of 5147; about half of the uses are in leave-on skin care products

(Table 3).

Potassium hydroxide has the second greatest number of overall uses reported, with a total of 1074; the majority of

the uses also are in leave-on skin care products. The results of the concentration of use survey conducted in 2014 by the

Council indicate calcium hydroxide has the highest reported maximum concentration of use; it is used at up to 13.2% in

rinse-off shaving preparations.

However, it is only used up to 0.5% in leave-on products (deodorants). Sodium hydroxide

and potassium hydroxide are used at up to 10% in leave-on skin preparations.

Some of these ingredients may be used in products that can be incidentally ingested or come into contact with

mucous membranes. For example, sodium hydroxide is used in lipstick (at up to 0.26%) and in bath soaps and detergents (at

up to 12.9%). Additionally, some of these ingredients were reported to be used in hair sprays and body and hand sprays and

could possibly be inhaled. For example, potassium hydroxide was reported to be used in hair sprays at a maximum

concentration of 0.69%. In practice, 95% to 99% of the droplets/particles released from cosmetic sprays have aerodynamic

equivalent diameters >10 µm, with propellant sprays yielding a greater fraction of droplets/particles below 10 µm compared

with pump sprays.

11-14

Therefore, most droplets/particles incidentally inhaled from cosmetic sprays would be deposited in the

nasopharyngeal and bronchial regions and would not be respirable (i.e., they would not enter the lungs) to any appreciable

amount.

12,13

The European Commission has added sodium hydroxide, potassium hydroxide, and calcium hydroxide to Annex III

List of Substances Which Cosmetic Products Must Not Contain Except Subject to the Restrictions Laid Down.

The uses of

sodium hydroxide and potassium hydroxide may not exceed 5% in nail cuticle solvents; 2% for general use and 4.5% in

professional use of hair; must have a pH below 12.7 when used as a pH adjuster in depilatories; and must have pH below 11

in other uses. The use of calcium hydroxide may not exceed 7% in hair straighteners containing calcium hydroxide and a

guanidine salt, must have a pH below 12.7 when used as a pH adjuster in depilatories, and must have a pH below 11 in all

other uses.

Magnesium hydroxide is not restricted from use in any way under the rules governing cosmetic products in the

European Union.

Non-Cosmetic

The inorganic hydroxides in this report are generally recognized as safe (GRAS) as direct food substances based

upon following current good manufacturing practice conditions of use (21CFR§184). Additionally, they are GRAS as feed

additives for animals (21CFR§582). The FDA has also reviewed calcium hydroxide and magnesium hydroxide for use as an

active ingredient in over-the-counter (OTC) drugs. Based on evidence currently available, there are inadequate data to

establish general recognition of the safety and effectiveness of this ingredient in certain drug products (21CFR §310).

Calcium hydroxide is used in mortar, plaster, cement and other building and paving materials.

It is also used in

lubricants, drilling fluids, pesticides, fireproofing coatings, water paints, as egg preservative, in the manufacture of paper

pulp, in rubber vulcanization in water treatment, as an absorbent for carbon dioxide, and in dehairing hides. Therapeutically,

it is used as an astringent.

Magnesium hydroxide may be used therapeutically as an antacid, cathartic, or laxative.

It is an approved OTC

active ingredient (21 CFR§ 331.11).

Non-cosmetic uses of potassium hydroxide include mordant for wood, mercerizing cotton, absorbing carbon

dioxide, removing paint and varnish, electroplating, photoengraving and lithography, printing inks, debudding calves’ horns

and dissolving scales and hair in skin scrapings.

Sodium hydroxide is a well-known strong base and is extremely corrosive. Sodium hydroxide solutions are used to

neutralize acids and make sodium salts (for example, in petroleum refining to remove sulfuric and organic acids); to treat

cellulose during viscose rayon and cellophane production; to reclaim rubber; in plastics manufacturing; and in dehorning

calves.

7,8

TOXICOKINETICS

No relevant published toxicokinetics studies on inorganic hydroxides were identified in a literature search for these

ingredients and no unpublished data were submitted.

TOXICOLOGICAL STUDIES

Acute Toxicity

Animal acute dose toxicity studies are presented in Table 4.

3-6,16-19

In oral toxicity studies, calcium hydroxide had an

> 7300 mg/kg bodyweight in rats and mice and magnesium hydroxide had an LD

> 2000 mg/kg bodyweight in rats.

An LD

of 1230 mg/kg bodyweight was observed in rats that received potassium hydroxide at doses that increased in log

fashion by factor of 2 starting at 0.1 mg/ml solution. Other oral studies of potassium hydroxide in rats have LD

results of

333 to 388 mg/kg bodyweight. Oral studies of sodium hydroxide led to extensive gastric damages in the animal tested. In

dermal toxicity studies, calcium hydroxide had an LD

>2.5 g/kg bodyweight in rabbits, and mice treated with 50% sodium

hydroxide had better survival rates with the test compound was washed off within an hour of application. In inhalation

studies in rats, the LC

s for magnesium hydroxide and sodium hydroxide were > 2.1 mg/l and > 0.75 mg/l, respectively.

Repeated Dose Toxicity

No relevant published repeated dose toxicity studies on inorganic hydroxides were identified in a literature search

for these ingredients and no unpublished data were submitted.

REPRODUCTIVE AND DEVELOPMENTAL TOXICITY

Magnesium Hydroxide

The reproductive effects of magnesium hydroxide (pH = 10) were studied in rats that received the test material via

gavage.

Groups of 10 male and 10 female Wistar rats received 0, 110, 330, or 1000 mg/kg bw/day magnesium hydroxide in

water daily. Males were exposed for 29 days (i.e. 2 weeks prior to mating, during mating, and up until treatment end) and

females were exposed for 41-45 days (i.e.2 weeks prior to mating, during mating, during post-coitum, and during at least 4

days of lactation). No treatment-related effects were observed on clinical signs, body weight or weight gain, feed

consumption, or hematology. In parental males, lower total protein levels (330 and 1000 mg/kg dose groups), lower albumin

levels (1000 mg/kg dose group), and lower calcium levels (330 and 1000 mg/kg dose groups) in the blood and lower sodium

and potassium excretion (1000 mg/kg dose group) and higher calcium concentration in urine (1000 mg/kg dose group) were

observed; however, these changes only just exceeded or remained within normal ranges and there were no corresponding

histopathological changes. No toxicologically relevant changes from the test material were observed in parental organ

weights or in gross pathology. There were no treatment related effects on reproduction development. The no observed

adverse effect level (NOAEL) for parental systemic effects, parental reproductive effects, and offspring effects in this one

generation rat study of magnesium hydroxide is 1000 mg/kg bw/day.

GENOTOXICITY

Genotoxicity studies are presented in Table 5.

3-6,20

Calcium hydroxide, magnesium hydroxide, and sodium

hydroxide were not genotoxic in several different in vitro assays. Potassium hydroxide was not genotoxic in one Ames test,

but results were ambiguous in another Ames test and a chromosome aberration test. Sodium hydroxide was not genotoxic in

in vivo mouse studies at up to 0.015M.

IRRITATION AND SENSITIZATION

Dermal Irritation

Sodium hydroxide is a corrosive material that can produce immediate coagulative necrosis resulting in considerable

tissue damage with ulceration and sloughing.

High concentrations can cause deep burns and readily denatures keratin.

Following exposure, the chemical must be removed quickly and completely in order to avoid further damage to the skin or

possible systemic injury.

Dermal irritation studies are presented in Table 6.

2-6,22-31

Magnesium hydroxide was not irritating or corrosive in in

vitro tests; however, potassium hydroxide and sodium hydroxide were corrosive at concentrations as low as 1%. Calcium

hydroxide was generally irritating but not corrosive in dermal rabbit studies. Potassium hydroxide was irritating and/or

corrosive in rabbit (at 2% or greater) and guinea pig (at 10%) studies. Sodium hydroxide was irritating/corrosive in a

concentration dependent manner in rat, rabbit, and pig studies. In humans, sodium hydroxide was irritating at concentrations

as low as 0.5%. Because of the large number of studies the include sodium hydroxide as a positive control, only a sampling

has been presented in this safety assessment.

Ocular Irritation

Caustic chemicals like sodium hydroxide can rapidly penetrate ocular tissues.

Toxicity is a function of pH, with

greater toxicity associated with increasing pH values. The concentration of the solution and duration of contact with the eye

are important determinants of the eventual clinical outcome.

Ocular irritation studies are presented in Table 7.

3-6,31-35

Calcium hydroxide was predicted to be irritating in hen’s

egg test-chorioallantoic membrane (HET-CAM) in vitro tests while magnesium hydroxide was predicted not to be irritating

in a bovine corneal opacity and permeability (BCOP) in vitro test. In rabbit studies, calcium hydroxide was severely

irritating at a concentration as low as 10% and pH of 9. Potassium hydroxide and sodium hydroxide were severely irritating

and/or corrosive in a concentration-dependent manner. Magnesium hydroxide was not irritating in a rabbit study.

Dermal Sensitization

Dermal sensitization studies are summarized in Table 8.

4-6

Potassium hydroxide (0.1%) was not sensitizing in a

guinea pig study while magnesium hydroxide in propylene glycol was sensitizing in a local lymph node assay (LLNA) when

tested at up to 50%. In a human repeat insult patch test (HRIPT), sodium hydroxide was not sensitizing when induced at up

to 1.0% and challenged at 0.125%, but irritation was observed.

CASE REPORT

No relevant case reports were discovered in the published literature regarding exposure to inorganic hydroxides in

cosmetic products; however numerous cases of accidental occupational or industrial exposures were reported.

3,4,6,36

SUMMARY

The inorganic hydroxides, calcium hydroxide, magnesium hydroxide, potassium hydroxide, and sodium hydroxide,

are all alkaline salts and function most commonly as pH adjusters in cosmetics. Inorganic hydroxides, with the exception of

magnesium hydroxide, are well known caustic agents that can cause severe burns and corrosion in acute exposures. Sodium

hydroxide is commonly used as a positive control in efficacy studies of skin protective creams and in other studies of irritant

contact dermatitis.

According to the 2015 VCRP survey data, sodium hydroxide has the most reported uses of the ingredients listed in

this safety assessment in cosmetic products, with a total of 5147; about half of the uses are in leave-on skin care products.

Potassium hydroxide has the second greatest number of overall uses reported, with a total of 1074; the majority of the uses

also are in leave-on skin care products. The results of the concentration of use survey conducted in 2014 by the Council

indicate calcium hydroxide has the highest reported maximum concentration of use; it is used at up to 13.2% in rinse-off

shaving preparations. However, it is only used up to 0.5% in leave-on products (deodorants). Sodium hydroxide and

potassium hydroxide are used at concentrations up to 10% in leave-on skin preparations.

The inorganic hydroxides in this report are GRAS as direct food substances and as feed additives for animals. The

FDA has also reviewed calcium hydroxide and magnesium hydroxide for use as an active ingredient in over-the-counter

drugs. Inorganic hydroxides have numerous non-cosmetic uses.

In oral toxicity studies, calcium hydroxide had an LD

> 7300 mg/kg bodyweight in rats and mice and magnesium

hydroxide had an LD

> 2000 mg/kg bodyweight in rats. An LD

of 1230 mg/kg bodyweight was observed in rats that

received potassium hydroxide at doses that increased in log fashion by a factor of 2 starting at 0.1 mg/ml solution. Other oral

studies of potassium hydroxide in rats have LD

results of 333 to 388 mg/kg bodyweight. Oral studies of sodium hydroxide

led to extensive gastric damages in the animal tested. In dermal toxicity studies, calcium hydroxide had an LD

>2.5 g/kg

bodyweight in rabbits, and mice treated with 50% sodium hydroxide had better survival rates when the test compound was

washed off within an hour of application. In inhalation studies in rats, the LC

s for magnesium hydroxide and sodium

hydroxide were > 2.1 mg/l and > 750 µg/l, respectively.

The NOAEL for parental and offspring effects following oral exposure to magnesium hydroxide (pH = 10) was

1000 mg/kg bw/day. No treatment-related effects were observed on clinical signs, body weight or weight gain, feed

consumption, or hematology. No toxicologically relevant changes from the test material were observed in parental organ

weights or in gross pathology. There were no treatment related effects on reproduction development.

Calcium hydroxide, magnesium hydroxide, and sodium hydroxide were not genotoxic in several different in vitro

assays. Potassium hydroxide was not genotoxic in one Ames test, but results were ambiguous in another Ames test and a

chromosome aberration test. Sodium hydroxide was not genotoxic in in vivo mice studies at up to 0.015M.

Magnesium hydroxide was not irritating or corrosive in in vitro tests; however, potassium hydroxide and sodium

hydroxide were corrosive at concentrations as low as 5%. Calcium hydroxide was irritating but not corrosive in dermal

rabbit studies. Potassium hydroxide was irritating and/or corrosive in rabbit and guinea pig studies at concentrations of 2%

or greater. Sodium hydroxide was irritating and/or corrosive in a concentration dependent manner in rat, rabbit, and pig

studies. In humans, sodium hydroxide was irritating at concentrations as low as 0.5%. Because of the large number of

studies that include sodium hydroxide as a positive control, only a sampling has been presented in this safety assessment.

Calcium hydroxide was irritating in HET-CAM in vitro tests while magnesium hydroxide was not irritating in a

bovine corneal opacity and permeability BCOP in vitro test. In rabbit studies, calcium hydroxide was severely irritating at a

concentration of 10% and pH of 9. Potassium hydroxide and sodium hydroxide were severely irritating and/or corrosive in a

concentration-dependent manner. Magnesium hydroxide was not irritating in a rabbit study.

Potassium hydroxide (0.1%) was not sensitizing in a guinea pig study while magnesium hydroxide in propylene

glycol was sensitizing in an LLNA when tested at up to 50%. In an HRIPT, sodium hydroxide was not sensitizing when

induced at up to 1.0% and challenged at 0.125%, but irritation was observed.

A case report detailed the presentation of a plumber with chronic eczema 2 years after accidental submersion of his

hands in sodium hydroxide solution.

No relevant published toxicokinetics or repeated dose toxicity studies on inorganic hydroxides were identified in a

literature search for these ingredients and no unpublished data were submitted.

DATA NEEDS

CIR is seeking types and concentrations of impurities and/or general composition of cosmetic-grade inorganic

hydroxides. Additional toxicological data, especially from dermal or ocular exposure, for ingredients at use concentration

would help the Panel assess the safe use of these ingredients in cosmetics.

TABLES

Table 1. Definitions, structures, and functions of the ingredients in this safety assessment.

Ingredient/CAS No.

Definition & Structure

Function

Calcium Hydroxide

1305-62-0

Calcium Hydroxide is the inorganic base that conforms to the formula

pH adjuster

Magnesium Hydroxide

1309-42-8

Magnesium Hydroxide is an inorganic base that conforms to the formula

absorbent; pH

adjuster

Potassium Hydroxide

1310-58-3

Potassium Hydroxide is the inorganic base that conforms to the formula

pH adjuster

Sodium Hydroxide

1310-73-2

Sodium Hydroxide is the inorganic base that conforms to the formula

denaturant;

pH adjuster

Table 2. Physical and chemical properties of inorganic hydroxides

Property

Value

Reference

Calcium Hydroxide

Physical form

crystals or soft, odorless granules or

powder with a slight bitter or alkaline

taste

Molecular weight (g/mol) 74.09

2.4

Specific gravity 2.08-2.34

Magnesium Hydroxide

Physical form bulky white, amorphous powder

Molecular weight (g/mol) 58.32

Melting point (

C) 350 (decomposes)

4.0

Specific gravity 2.36

Solubility at 25

C, mg/l 11.7

Potassium Hydroxide

Physical form

White or slightly yellow lumps, rods,

pellets

Molecular weight (g/mol) 56.11

Melting point (

C) 360

0.5

Specific gravity 2.044

Sodium Hydroxide

Physical Form

Brittle, white, translucent crystalline

solid

Molecular Weight ( g/mol) 39.998

Melting point (

C) 318

Boiling point

C at 760 mm Hg 1388

0.2

Specific gravity at 20 °C 2.13

Table 3. Frequency and concentration of use according to duration and type of exposure for inorganic hydroxide.

9,10

# of Uses Max Conc of Use (%)

# of Uses

Max Conc of Use

(%)

Calcium Hydroxide

Magnesium Hydroxide

Totals

†

0.1-13.2

1.1-1.6

Duration of Use

Leave-On

0.11-0.5

Rinse Off

0.1-13.2

1.1-1.6

Diluted for (Bath) Use

Exposure Type

Eye Area

Incidental Ingestion

Incidental Inhalation -Sprays

spray: NR

possible: 2

; 1

spray: NR

possible: 0.18

Incidental Inhalation - Powders

powder: NR

possible: 1

powder: 1

Dermal Contact

0.1-13.2

1.1

Deodorant (underarm)

spray: NR

possible: NR

not spray: 0.5

Hair - Non-Coloring

0.18-6

Hair-Coloring

1.6

Nail

Mucous Membrane

1.1

Baby Products

Potassium Hydroxide

Sodium Hydroxide

Totals

†

1074

0.0000049-10

5147

0.0000083-12.9

Duration of Use

Leave-On

681

0.0000049-10

2802

0.0000083-10

Rinse Off

387

0.00048-7.2

2267

0.00002-12.9

Diluted for (Bath) Use

0.3-6.4

0.00002-0.28

Exposure Type

Eye Area

0.000049-0.5

191

0.0000083-0.86

Incidental Ingestion

0.00049-0.005

0.00083-0.26

Incidental Inhalation -Sprays

spray: 9

possible: 252

; 240

spray: 0.00049-0.69

possible: 0.0045-

0.77

; 0.3-10

spray: 13

possible: 1284

;

745

spray:

0.000025-0.35

possible: 0.0025-

0.93

; 0.09-2

Incidental Inhalation - Powders

powder: NR

possible: 240

; 3

powder: 0.0000049

possible: 0.3-10

powder: 2

possible: 745

; 16

powder:

0.0000083-0.25

possible: 0.09-2

Dermal Contact

995

0.0000049-10

4310

0.0000083-12.9

Deodorant (underarm)

spray: NR

possible: 3

spray: NR:

possible: 129

spray: 0.4

possible: NR

not spray: 0.01-1.1

Hair - Non-Coloring

0.005-0.77

444

0.00002-3

Hair-Coloring

0.31

329

0.001-1.7

Nail

0.02-1.7

0.13-1

Mucous Membrane

102

0.00049-6.4

1253

0.00002-12.9

Baby Products

0.19-0.21

0.13-0.16

NR = Not reported.

† Because each ingredient may be used in cosmetics with multiple exposure types, the sum of all exposure types may not equal the sum of total

uses.

It is possible these products may be sprays, but it is not specified whether the reported uses are sprays.

Not specified whether a powder or a spray, so this information is captured for both categories of incidental inhalation.

It is possible these products may be powders, but it is not specified whether the reported uses are powders.

Table 4. Acute toxicity studies

Ingredient

Concentration/Dose

Study Protocol

Results

Reference

Oral

calcium hydroxide

details not provided

oral study in mice and rats (no

further details provided)

> 7300 mg/kg

bodyweight

magnesium hydroxide in

water

2000 mg/kg

oral gavage (10 ml/kg dose volume)

in 3 female Wistar rats

> 2000 mg/kg

bodyweight

potassium hydroxide

details not provided

oral gavage in male Sprague Dawley

rats 14 day conventional test (10

animals/dose) or 1 week up-and-

down test (1 animal/dose)

= 333 mg/kg

bodyweight in

conventional method,

= 388 mg/kg

bodyweight in up-and-

down test

potassium hydroxide in

water

0.1 mg/ml solution with

doses increased in log

fashion by factor of 2

oral gavage in 5 male/dose Carwoth-

Wistar rats

= 1230 mg/kg

bodyweight

potassium hydroxide

details not provided

oral gavage in 9 male/dose Charles

River albino rats

= 365 mg/kg

bodyweight

sodium hydroxide

0.2 N

oral study in rats (no further details

provided)

Extensive damage to

gastric mucosa observed

sodium hydroxide

8.3%

oral study in cats (no further details

provided)

Superficial layer of

squamous mucosa was

destroyed; submucosal

and transmural

thrombosis observed in

the blood vessels

sodium hydroxide

7 ml of 0.5 N

oral gavage in 26 Wistar rats (no

further details provided)

Entire gastric mucosa fell

off; intestinal metaplasia

in 18/26 rats

sodium hydroxide in

water

0.4%, 0.5%, or 0.62%

corresponding to 20, 25,

or 31 mg/kg bodyweight

oral study in male rats ( no further

details provided)

Increasing concentrations

resulted in increasing

gastric injury; erosion

scores were 10%, 65%,

and 70% for 0.4%, 0.5%,

and 0.62% NaOH,

respectively

Dermal

calcium hydroxide

2.5 g/kg bodyweight

dermal exposure to 5 male and 5

female New Zealand White rabbits;

patches semi-occluded; test area 100

; test site rinsed with water after

24 h

> 2.5 g/kg

bodyweight

sodium hydroxide in

water

50%

Dermal exposure in groups of 27

54A/He and C57 black mice, test

sites were irrigated immediately, or

after 30 min, 1 h, 2 h, or not at all

(no further details provided)

Mortality rate of the mice

was 0%, 20%, 40%, 80%,

and 71% when

application sites were

irrigated immediately,

after 30 min, after 1 h,

after 2 h, or not at all

Inhalation

magnesium hydroxide

2.1 mg/l

4-h whole-body inhalation of aerosol

in groups of 5 male and female

Wistar rats

> 2.1 mg/l

sodium hydroxide

0.75 mg/l

whole body exposure of aerosol for

2 h in 24 male Wistar rats,

microscopic examinations performed

on cross sections of nose, larynx,

trachea with esophagus, and lungs at

1 h and 24 h post-exposure

No mortalities during test;

acute laryngitis observed

in 11 animals after 1 h

and after 24 h; average

severity of lesions was

1.58 (very slight) at 1 h

and 1.25 (very slight) at

24 h

Table 5. Genotoxicity studies

Ingredient

Concentration/Dose

Study Protocol

Results

Reference

In Vitro

calcium hydroxide

0.3 to 3750 µg/plate

Ames test in Salmonella typhimurium

strains TA 98, TA100, TA 1535, and

TA 1537 and Escherichia coli strain

WP2 uvr A, with and without

metabolic activation

-not mutagenic

calcium hydroxide in

glycerol

30, 100, or 300 mM

-chromosome aberration study, with

and without metabolic activation, in

human dental pulp cells

-test material was incubated with cells

in one of 3 scenarios: 30 h continuous

treatment with colcemid added 3 h

before harvest; 3 h treatment with 27 h

recovery and colcemid added 3 h

before harvest; or 2 h treatment with a

28 h recovery and colcemid added 3 h

before harvest (metabolic activation

scenario)

-not genotoxic

magnesium hydroxide in

dimethyl sulfoxide

(DMSO)

100 to 5000 µg/plate

Ames test in S. typhimurium strains

TA 98, TA 100, TA 1535, and TA

1537 and E. coli strain WP2 uvr A,

with and without metabolic activation

-not mutagenic

magnesium hydroxide in

DMSO

1, 3, 10, or 33 µg/ml

mouse lymphoma L5178Y/TK

mutation test, with and without

metabolic activation

-not mutagenic

-test material precipitated

at concentrations greater

than 33 µg/ml

magnesium hydroxide in

DMSO

3, 10, or 33 µg/ml

chromosome aberration test in human

lymphocytes, with and without

metabolic activation

-not clastogenic

-test material precipitated

at concentrations greater

than 33 µg/ml

potassium hydroxide in

distilled water

0.01, 0.05, 0.1, 0.5, or 1

mg/plate

Ames test in S. typhimurium strains

TA 97 and TA 102, with and without

metabolic activation

not genotoxic

potassium hydroxide in

distilled water

0.00945% to 0.019%

Ames test in E. coli strains B/Sd-4/3,4

and B/Sd-4/1,3,4,5 without metabolic

activation

-ambiguous results (no

further details)

potassium hydroxide

0, 4, 8, 12, 16, or 20 mM

Chinese hamster ovary (CHO)

chromosome aberration test, with and

without metabolic activation

-ambiguous results:

positive with metabolic

activation at 12 mM and

pH 10.4 but negative

without metabolic

activation

-genotoxic effects due to

high non-physiolocial pH

that may yield false-

positive results

sodium hydroxide

details not provided

Ames test in S. typhimurium strains

TA 98, TA 100, TA 1535, TA 1537,

TA 1538 ( no further details provided)

not genotoxic

sodium hydroxide

0, 4, 8, or 16 mM with

corresponding pH values

of 7.4, 9.1, 9.7, or 10.6,

respectively

CHO-K1 cell chromosomal aberration

test, with and without metabolic

activation

not clastogenic

sodium hydroxide

details not provided

unscheduled DNA synthesis assay in

E. coli strains WP2, WP67, CM871

(no further details provided)

not genotoxic

sodium hydroxide

details not provided

unscheduled DNA synthesis assay in

E. coli strains WP2, WP2uvrA,WP67,

CM611, WP100, W3110polA+,

p3478pola-, with and without

metabolic activation (no further details

provided)

not genotoxic

In Vivo

sodium hydroxide (as a

control substance)

10 mg/kg of 15 mM

Chromosome aberration micronucleus

assay in 5 male and 5 female CD-

mice via a single intraperitoneal dose

-no significant increase of

nuclei was observed

sodium hydroxide (as a

control substance)

0.3-0.4 ml of 0.01 M

Aneuploidy induction study in female

Swiss mice; mice injected

intraperitoneally and chromosome

spreads were made 12 h after injection

(no further details provided)

-no non-disjunction

observed

Table 6. Dermal irritation studies

Ingredient

Concentration/

Study Protocol

Results

Reference

Non-Human In Vitro

magnesium hydroxide

details not provided

Human three dimensional epidermal

model using 10 mg test material

moistened with 25 µl purified water

Not irritating

magnesium hydroxide

details not provided

Human three dimensional epidermal

model using 25 mg test material

moistened with 25 µl purified water

Not corrosive

potassium hydroxide

10%

Epiderm and Skin

ZS1301 in vitro

models (validation study)

Corrosive

(Perkins 1996)

potassium hydroxide

5% and 10%

In vitro skin corrosion –

transcutaneous electrical resistance

test (TER) (validation study)

Corrosive at both

concentrations tested

(Fentem 1998)

potassium hydroxide

5% and 10%

Skin

ZK1350 in vitro model

(validation study)

Corrosive at 10%, non-

corrosive at 5%

(Fentem 1998)

potassium hydroxide

Leiden human reconstructed

epidermal in vitro model (validation

study)

Corrosive and irritant

(El Ghalbzouri

2008)

potassium hydroxide

5% and 10%

In vitro membrane barrier test

method (validation study)

Corrosive at both

concentrations tested

(Ferntem 1998)

potassium hydroxide

SkinEthic in vitro model

Irritant

(Tornier C 2006)

potassium hydroxide

5% and 10%

Episkin model (validation study)

Corrosive at both

concentrations tested

(Fentem 1998)

potassium hydroxide

10%

SkinEthic reconstituted human

epidermal model (validation study)

Corrosive

(Kandarova 2006)

sodium hydroxide in

water

4.9%

Skin

ZK1350 in vitro model

Corrosive

(Liebsch 1995)

sodium hydroxide in

water

16% and 24%

-irritation study in Yorkshire

weanling pigs skin flaps

-test area was 5 cm

area on the

lower abdominal skin

-dose volume = 200 µl

Severe necrosis of all

epidermal cell layers and

dermis, with some lesions

extending into the

subcutaneous layers. A

decrease in glucose

utilization and changes in

vascular resistance were

observed

(Srikrishna 1991)

sodium hydroxide

-in vitro study using human breast

or abdominal tissues

-test material (150 µl) applied to the

epidermis of at least 6 skin discs for

24 h before rinsing with water

-transcutaneous electrical resistance

(TER) was measured

Corrosive effects

observed (TER was

below 11.0 kohms/disc at

7.7)

Non-Human In Vivo

calcium hydroxide

details not provided

-irritation study in 3 Himalayan

rabbits

-treated skin was cleaned with soap

and water immediately after

exposure

-0.5 g test material applied to

shaved skin for 4 h

-sites graded immediately and at 1,

24, 48, and 72 h and on days 7 and 4

post-exposure

Irritating but not

corrosive

calcium hydroxide

details not provided

-Draize irritation study in 3 New

Zealand White rabbits

-0.5 g test material applied to

shaved skin and semi-occluded for 4

-sites graded at 1, 24, 48, and 72 h

post-patch removal

Not irritating

calcium hydroxide

details not provided

-5 male and 5 female New Zealand

White rabbits

-2500 mg/kg applied via semi-

occluded patches on shaved skin for

24 h

-treated skin was rinsed with water

24 h after application

Irritating; redness

followed by scabbing,

was observed at the test

site following rinsing

potassium hydroxide

1% and 2%

-Draize irritation study in 6 rabbits

-occlusive 1 in

patches on clipped

skin

-0.5 ml applied for 4 h

Not corrosive at 1%,

corrosive at 2%

Table 6. Dermal irritation studies

Ingredient

Concentration/

Study Protocol

Results

Reference

Non-Human In Vivo (Continued)

potassium hydroxide

10%

-irritation study in 6 Hartley guinea

pigs

-0.5 ml test material on intact and

abraded skin for 4 h, patches

occluded

-sites graded after 4, 24, and 48 h

Corrosive

(Nixon 1975)

potassium hydroxide

5% and 10%

-6 rabbits exposed to 0.2 ml test

material in 19 mm diameter Hill

Top chamber for 1 or 4 h or 0.5 ml

on Webril gauze patches for 4 h

-patches occluded

-sites graded 30 min, 24, 48, and 72

h after patch removal

Severe irritation at both

concentrations tested

(Nixon 1990)

potassium hydroxide

10%

-irritation study in 6 rabbits

-0.5 ml test material applied under

occlusive patches on abraded and

intact skin for 4 h

-sites observed after 4, 24, and 48 h

Corrosive

(Nixon 1975)

potassium hydroxide

-modified Draize study in 6 albino

rabbits

-0.1 ml test material applied to area

of 20 mm

for 24 h under occlusive

patches on abraded and intact skin

Mild irritant on intact

skin, extreme irritant on

abraded skin

sodium hydroxide

details not provided

-stepwise screening test for skin

irritation in mice (no further details

provided)

-minimum concentration

for skin irritation was 5%

(50 mg/kg)

-minimum intradermal

test response was 0.25%

to 0.3% (1.25-1.5 mg/kg)

sodium hydroxide

-test material was applied for 1 min

with 2 cm diameter filter paper to

the abdomens of 20 SD rats

-test area was washed with 500 ml

distilled water at 1, 10, or 30 min

post-exposure

-test sites examined at 1-min

intervals for up to 90 min

-subcutaneous tissue pH

did not recover to pre-

experiment values by the

min

-tissue pH value did not

exceed 8.0 (at 1 min)

-no difference in effects

were observed when

washing was at 10 or 30

min

(Yano 1993)

sodium hydroxide

0.36% and 5%

-test material (0.5 ml) was applied

for 4 h to 4 New Zealand White

rabbits

-semi-occluded patches on clipped

dorso-lumbar skin

-test sites washed after patch

removal

-test sites examined 1, 24, 48, 72,

and 144 h after patches were

removed

-test material was

corrosive at 5% when

tested in 1 rabbit, scores

of 4 for erythema were

recorded up to 168 h

post-patch removal,

edema scores of 1 were

recorded at 24 and 48 h

-no irritation was

observed in 3 rabbits at

0.36%

sodium hydroxide

4.9% by weight

Irritation study in 3 Vienna White

rabbits (1 male, 2 females); patches

were occlusive and applied to

shaved skin (one intact and one

abraded site) for 24 h; sites

observed for reactions at 24 and 72

h post-application with last check

after 8 days

Moderately irritating with

a primary irritation index

(PII) score of 5.6; mild

necrosis was observed

after 24 h and parchment-

like/leather-like necrosis

was observed after 72 h

that was observed after 8

days

sodium hydroxide

1% w/v aq. solution

Irritation study in 6 New Zealand

White rabbits; patches were 2.5 cm

and the shaved sites were occluded

for 2 h; sites observed for reactions

at 1, 24, 48, 72 h and 7 days

Slight skin irritant; very

slight erythema in 2

animals at 1 h, well-

defined reaction observed

in 1 animal and same

very slight irritation in 2

other animals at 24 h;

very slight irritation

observed in 3 animals at

48 and 72 h that persisted

in 1 animal until day 7

Table 6. Dermal irritation studies

Ingredient

Concentration/

Study Protocol

Results

Reference

Non-Human In Vivo (Continued)

sodium hydroxide

0.95% by weight

Irritation study in 3 female Vienna

White rabbits; patches were

occlusive and applied to shaved skin

(one intact and one abraded site);

sites observed for reactions at 24

and 72 h post-application with last

check after 8 days

Mildly irritating with a

PII score of 2.7; fully

reversible erythema in 2

rabbits with spot-like

necrosis observed at 72 h

for 2 animals

sodium hydroxide

5% aqueous

Irritation study in 6 New Zealand

White rabbits exposed for 2 h to 0.5

ml test material; test site was 2.5

, shaved and occluded; sites

were scored at 24, 48, and 72 h and

on day 7

Skin irritant; Slight

dermal irritation observed

in 3 animals 1 h post-

patch removal; 1 rabbit

had caustic burn with “in

depth” skin damage and

small dermal

hemorrhages; 2 rabbits

had small dermal

hemorrhages with some

slight tissue necrosis;

similar reaction observed

at 24, 48, and 72 h and on

day 7; one patch had poor

skin contact during the 2

h patching

sodium hydroxide in

water

8%, 16% or 24%

-irritation study in 4 Yorkshire

weanling pigs

-200 µl on a 5 cm

area on the lower

abdominal skin for 30 min

-highly irritating at 8%

and 16%, corrosive at

24%

-gross blisters developed

within 15 min of

application

-8% and 16% produced

severe necrosis in all

epidermal layers

-24% produced numerous

and severe blisters with

necrosis extending into

the subcutaneous tissue

(srikrishna 1991)

Human

sodium hydroxide

0.5% in aq. solution

-test material (50 µl) used as a

positive control and irritation

inducer in an efficacy study of skin

protective creams in 20 human

subjects

-test material applied on 18 mm

diameter area on 5/13 test sites

-yielded expected

irritation as a positive

control

sodium hydroxide

0.5%

Patch test in 30 subjects with 0.2 ml

of the test substance on a 25 mm

Plain Hill Top Chamber containing

a Webril pad for 15 and 30 min, 1,

2, 3, and 4 h.

Irritating to the skin,

maximum exposure time

was limited to 1 h due to

strong level of response

sodium hydroxide

2% in distilled water

Closed patch test in 12 mm diameter

Finn chambers of experimental

irritants in 16 subjects; patch was

removed after 1h

Visual median score after

24 h and 96 h was 1 out 3

(weak positive reaction),

respectively

Table 6. Dermal irritation studies

Ingredient

Concentration/

Study Protocol

Results

Reference

Human (Continued)

sodium hydroxide

up to 5% aq.

-patch test in healthy male

volunteers of 7 known irritants to

determine the optimum

concentration to produce mild to

moderate reactions in ~75% of

individuals tested;

-test substance (30 µl/cm

) applied

to the volar area of the forearm with

8 mm Finn chambers;

-patches removed after 48 h and

reactions assessed 1 h later.

-0% of the subjects had a

positive reaction at 1%,

29% of the subjects had a

positive reaction at 2%,

and 100% of the subjects

had a positive reaction at

4%;

-at 2%, 4 subjects had +/-

reactions;

-at 3%, 2 subjects had +/-

reactions, 1 subject had

1+ reaction, and 4

subjects had 2+ reaction;

-at 5%, 2 subjects had 3+

reaction and 1 subject

had 4+ reaction;

-the severity of irritant

reactions to sodium

hydroxide rose sharply

with increasing

concentration, with

considerable pain in some

volunteers, that led to

removing the patches

before 48 h.

sodium hydroxide

0.5% dissolved in water

-test material was used as a positive

control and irritation inducer in an

efficacy study of

perflurorpolyethers as protective

preparations;

-7 male and 3 female subjects;

-irritant application of 0.05 ml

occurred 30 min after pretreatment

with protective preparation in 12

mm diameter Finn chambers;

-chambers removed after 30 min of

exposure and the skin was rubbed

dry;

-subjects were treated over a 12-day

period.

-sodium hydroxide

yielded expected

irritation as a positive

control

sodium hydroxide

0.5% dissolved in water

-test material was used as a positive

control and irritation inducer in an

efficacy study of

perflurorpolyethers as protective

preparations;

-7 male and 13 female subjects;

-irritant application of 0.05 ml

occurred 30 min after pretreatment

with protective preparation in 12

mm diameter Finn chambers;

-chambers removed after 30 min of

exposure and the skin dried;

-subjects were treated over a 12-day

period.

-sodium hydroxide

induced significant

irritant reaction from day

1 until the end of the first

week, and to a smaller

extent from end of week1

to the end of week 2, as

indicated by visual score

values, transepidermal

water loss (TEWL), and

chromametry of the

control sites.

sodium hydroxide

2% in sterile water, pH

13.7

-closed patch test of different

irritants in 16 volunteers (10 female,

6 male) on both arms using 12 mm

diameter Finn chambers;

-skin damage was evaluated visually

and by polysulfide rubber replica;

-sodium hydroxide patch was

removed at the most 1 h post-

application;

-visual assessments of the test sites

were performed 24, 48, and 96 h

post-application;

-skin surface imprints with

polysulfide rubber were made.

-at 24 h, reactions were

observed in 12 subjects

with 3 being scored a 3;

-at 48 h, reactions were

observed in 9 subjects

with 5 being scored a 3;

-at 96 h, reactions were

observed in 11 subjects

with 4 being scored a 3;

-in 31% of the imprints,

skin damage was

observed

Table 6. Dermal irritation studies

Ingredient

Concentration/

Study Protocol

Results

Reference

Human (Continued)

sodium hydroxide

1 g/v% in distilled

water, pH 12.7

-test of barrier function of the skin

following exposure to low

concentrations of known irritants;

-allergic patch testing in 42 subjects

with miscellaneous diseases;

-test sites were on unaffected skin of

the volar forearm;

-test substance (100 µl) was applied

for 48 h by 12 mm Finn chambers;

-24 h post-exposure, the skin water

vapor loss was measured.

-sodium hydroxide was

observed to increase skin

water vapor loss when

compared to unexposed

skin (3.6 g/m

h + 2.0, p

< 0.05).

sodium hydroxide

0.5 mol/l

-19 subjects received two 30 min

exposures/day with a 3-h interval

for 4 days

-50 µl test material via occlusive

(Finn Chambers or Scanpor 12 mm

diameter discs) and non-occlusive

patches

-test sites were rinsed with 10 ml of

tap water and dried after the 30 min

applications

-highly irritating

-application of test

material was

discontinued after the 3

day because of the

severity of the reactions

-increased in TEWL

values observed at day 3

-visual scores showed

highly significant

irritation

Table 7. Ocular irritation studies

Ingredient

Concentration

Study Protocol

Results

Reference

Non-Human – In Vitro

calcium hydroxide

50 mg, no further

details provided

-HET-CAM in vitro test

-irritating

calcium hydroxide

250 mg, no further

details provided

-HET-CAM in vitro test

-irritating

magnesium hydroxide

in physiological saline

details not provided

-BCOP in vitro test

-not irritating

-irritancy score was 501 after

240 min of treatment

Non-Human – In Vivo

calcium hydroxide

150g/l

-acute eye irritation/corrosion study

in 3 male New Zealand White

rabbits

-0.1 ml instilled into the

conjunctival sac of one eye, eye

was not rinsed

-observations made at 1, 24, 48,

and 72 h after treatment up to 21

days

-irritating

calcium hydroxide

10%, pH 9

-acute eye irritation/corrosion study

in 1 male New Zealand White

rabbit

-100 mg instilled into the

conjunctival sac

-eyes examine after 1 h

-irritating

-very severe reactions were

observed 1 h after exposure,

with pronounced chemosis,

necrotized appearance of the

conjunctiva, whitish watering

and total opacity of the cornea,

showing nacreous appearance

-iris became totally obscured

-test was discontinued after

treatment with 1 rabbit for

humanitarian reasons.

calcium hydroxide

0.01, 0.03, or 0.10 g, no

further details provided

-acute eye irritation/corrosion study

in New Zealand White rabbits

-9 rabbits received low dose, 6

rabbits each received medium and

high doses

-test material applied directly to the

cornea of one eye of each rabbit

-observations made a 1, 3, 7, 14,

and 21 days after treatment

-irritating

-study halted at 14 days for the

medium and high dose groups

due to severe eye irritation

-expected return to normalcy in

the eye of the low dose group

was greater than 21 days.

magnesium hydroxide

details not provided

-acute eye irritation/corrosion study

in 3 male New Zealand White

rabbits

-rabbits received an average

instillation of 57.3 mg (dose

volume 0.1 ml) of the test

substance in the conjunctival sac of

one eye, eye was not rinsed

-observations made at 1, 24, 48,

and 72 h after instillation

-not irritating

-slight dulling of normal luster

and/or epithelial damage in 2

rabbits resolved within 24 or 48

-iridial irritation grade 1

observed in all rabbits resolved

within 24h

-irritation of the conjunctivae

consisting of redness, chemosis,

and discharge in all rabbits

resolved within 72 h

potassium hydroxide in

water

0.1%, 0.5%, 1%, 5%

- acute eye irritation/corrosion

study in 10 albino rabbit eye

-0.1 ml instilled for 5 min or 24 h,

with observations performed at 1,

24, 48, and 72 h and 7 days

-eyes rinsed following exposure

-highly corrosive at 5% for 5

min (1 rabbit)

-irritant at1% for 5 min (3

rabbits)

-marginal irritant at 0.5% for 24

h (3 rabbits)

-no ocular reactions at 0.1% for

24 h (3 rabbits)

sodium hydroxide in

water

1.0% or 2.0%

- acute eye irritation/corrosion

study in 6 New Zealand White

rabbits

-0.1 ml instilled into lower

conjunctival sac

-observations made a 4, 24, 48, 72,

and 96 h

-2% caused moderate corneal

injury (score = 2.0 out of 4);

severe conjunctival irritation

was observed between 4 and 96

-lesser effects were observed

with the 1% solution (no further

details provided)

Table 7. Ocular irritation studies

Ingredient

Concentration

Study Protocol

Results

Reference

sodium hydroxide in

water

0.5% or 10%

- acute eye irritation/corrosion

study in New Zealand White

rabbits

-3 groups of 3 rabbits for 0.5%; 4

groups of 3 rabbits for 10%

-0.5% groups received 0.01, 0.03,

or 0.1 ml

-10% groups received 0.003, 0.01,

0.05 ml, or 0.1 ml

-observations made at 1 h and 1, 2,

3, 4, 7, 14, and 21 days

-eyes were not washed

-slight eye irritant at 0.5%,

corrosive at 10%

-at 0.5%, no corneal effects at

0.01-0.1 ml; grade 1 iridial

effects observed in 2/3 animals

that cleared by day 1 at 0.1ml

-at 10%, irreversible effects on

the eye at 0.05 and 0.1 ml

sodium hydroxide

details not provided

-eye irritation study in rats (no

details provided)

-eye irritation observed at a

concentration of 1.25%

sodium hydroxide in

distilled water

0.004% (0.001 M) ,

0.04% (0.01 M), 0.2%

(0.05 M), 0.4% (0.1M),

1.2% (0.3 M)

- acute eye irritation/corrosion

study in a minimum of 7 Stauffland

albino rabbits

-0.1 ml instilled into the lower

conjunctival sac

-observations made 1, 2, 3, 4, 7

days, then every 3-4 days up to 21

days post-treatment

-non-irritating at 0.004%-0.2%

-mild irritation at 0.4%

-corrosive at 1.2%

sodium hydroxide in

water

0.1%, 0.3%, 1.0%, or

3.0% corresponding to

pH values of 12.3, 12.8,

13.1, or 13.5

- acute eye irritation/corrosion

study in New Zealand albino

rabbits

-2 groups of 6 rabbits; eyes were

washed 30 sec after exposure for 2

min with 300 ml tap water and eyes

were unwashed after exposure in

the second

-0.1 ml instilled into conjunctival

sac

-observations made 1 h and 1, 2, 3,

and 7 days post-treatment

-conjunctivitis observed at 1.0%

and 3.0% that lasted through day

-duration of corneal opacities

produced by 1.0% reduced as a

result of washing test eyes 30 s

after instillation

Table 8. Sensitization studies

Ingredient

Concentration

Study Protocol

Results

Reference

Non-Human

potassium hydroxide in

water

0.1%

Intracutaneous repeat insult test in

5 male albino guinea pigs

not sensitizing

magnesium hydroxide

in propylene glycol

0%, 10%, 25%, or 50%

Local lymph node assay (LLNA)

in groups of 5 female CBA/J mice

-sensitizing

-SI values for 10%, 25%,

and 50% were 2.0, 3.6,

and 5.9, respectively

-EC

value calculated to

be 19.4%

Human

sodium hydroxide

induction 0.63% to

1.0%; challenge 0.125%

modified HRIPT in 15 male

subjects

-not sensitizing

-irritation response well

correlated with the

concentration of the

irritant

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